US4435427A - Stable injectable β-carotene micellar solutions and their preparation - Google Patents
Stable injectable β-carotene micellar solutions and their preparation Download PDFInfo
- Publication number
- US4435427A US4435427A US06/329,124 US32912481A US4435427A US 4435427 A US4435427 A US 4435427A US 32912481 A US32912481 A US 32912481A US 4435427 A US4435427 A US 4435427A
- Authority
- US
- United States
- Prior art keywords
- carotene
- emulsifier
- weight
- ionic
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Definitions
- the present invention relates to stable injectable micellar solutions of ⁇ -carotene and a process for their preparation.
- ⁇ -Carotene has the chemical formula: ##STR1##
- ⁇ -Carotene dificiency has hitherto been treated by feeding animals with carotene-rich straight fodder, such as lucerne green meal, grass green meal or carrots, and/or dry synthetic ⁇ -carotene powder.
- carotene-rich straight fodder such as lucerne green meal, grass green meal or carrots
- dry synthetic ⁇ -carotene powder such as lucerne green meal, grass green meal or carrots
- oral administration of ⁇ -carotene has little effect on its level in blood, because absorption of ⁇ carotene from the intestinal tract is poor.
- the blood level can be increased rapidly and over a relatively long period by parenteral administration of ⁇ -carotene.
- the formulations to be injected should have a relatively high content of ⁇ -carotene in extremely finely divided form, so that the volume to be injected is kept to a minimum.
- German Published Application DAS No. 1,210,127 discloses carotene emulsions containing polyoxyethylated castor oil or polyoxyethylene sorbitan fatty acid esters as emulsifiers, together with ionic wetting agents. However, these emulsions are not stable for a prolonged period, since the carotene crystallizes out.
- German Laid-Open Application DOS No. 2,236,899 therefore proposes the preparation of more highly concentrated emulsions using special soaps, namely soaps of tris-(hydroxymethyl)-aminomethane and saturated or unsaturated fatty acids of 9 to 20 carbon atoms.
- special soaps namely soaps of tris-(hydroxymethyl)-aminomethane and saturated or unsaturated fatty acids of 9 to 20 carbon atoms.
- the method proposed in that Application is not satisfactory, since on the one hand the procedure presents difficulties in practice, and on the other hand only water-miscible carotenoid emulsions containing not more than 4% of ⁇ -carotene can be prepared.
- this object is achieved by a process for the preparation of ⁇ -carotene miscellar solutions wherein a non-ionic emulsifier which is suitable for the preparation of micellar solutions is heated at from 160° to 180° C. and a total of from 20 to 30% by weight, based on the emulsifier, of ⁇ -carotene is introduced in the presence of a conventional antioxidant, the hot homogeneous mixture is cooled rapidly to below 100° C. by adding water, and the formulation is brought to the desired concentration of from 3 to 6% by weight by adding further water, and by the stable injectable ⁇ -carotene micellar solutions obtainable by this process.
- Non-ionic emulsifiers which are suitable for the preparation of micellar solutions are those having an HLB value (cf. H. P. Fiedler, Lexikon der Pharmazie, Kosmetik und angrenzenden füre, 1971, pages 263-270, especially pages 267-69) of from 12 to 16, especially oxyethylated triglycerides of fatty acids of 12 to 18 carbon atoms containing 20-60 oxyethylene units, oxyethylated sorbitan fatty acid esters having about 20 oxyethylene units, or oxyethylated monohydroxy-fatty acids having from 14 to 17 oxyethylene units, such as are disclosed in German Laid-Open Application DOS No. 2,911,241.
- Such emulsifiers are also called solubilizers, because they are soluble in water and thereby act as solubilizing agents for lipophilic substances by keeping these in micellar solution. Micellar solutions are transparent and clear.
- non-ionic emulsifiers examples include: glyceryl polyoxyethylene glycol ricinoleate, glycerol polyoxyethylene glycol hydroxystearate, polyoxyethylene-20 sorbitan mono-oleate, polyoxyethylene-20 sorbitan monostearate and the adduct monohydroxystearic acid with 15 units of ethylene oxide.
- micellar solutions are prepared by adding from 20 to 30% by weight, based on the emulsifier, of ⁇ -carotene a little at a time to the emulsifier, which is heated at from 160° to 180° C. and contains conventional antioxidants, whereupon the ⁇ carotene melts and dissolves virtually immediately.
- the mixture is rapidly brought to below 100° C. by adding water, and the formulation is then brought to the desired concentration by adding further water. After filtration and cooling to room temperature, a stable 4-6% preferably about 5%, strength by weight transparent micelllar solution is obtained, which is still stable after 12 months.
- antioxidants which can be used in the process according to the invention are butylhydroxytoluene, butylhydroxyanisole and d,l- ⁇ -tocopherol.
- the antioxidants are generally used in amounts of from 10 to 20% by weight, based on the ⁇ -carotene employed.
- Chromophor EL® glycerolpolyoxyethyleneglycol ricinoleate
- 6 g of butylhydroxytoluene 300 g
- the mixture is heated to an internal temperature of 160° C., whilst being stirred and gassed with nitrogen.
- 66 g of ⁇ -carotene are added in the course of about 5 minutes.
- the heating bath is removed and water is added dropwise until the internal temperature of the mixture has fallen to 100° C.
- the mixture is brought to 60°-80° C. by rapid addition of the remainder of the water (total amount: 828 g) and by using the heating bath.
- the still warm micellar solution is filtered through a glass filter frit to give an about 5% strength transparent ⁇ -carotene solution which can be used as an injection solution.
- Group 1 received 10 ml of an aqueous ⁇ -carotene micellar solution according to the invention, containing 450 mg of ⁇ -carotene, intramuscularly.
- Group 2 received an intramuscular injection of an oily ⁇ -carotene solution containing 450 mg of ⁇ -carotene.
- Group 3 received no ⁇ -carotene injection.
- the average plasma levels of ⁇ -carotene ( ⁇ g/100 ml) in the test animals were measured before the treatment and 1, 2, 4 and 32 days after the treatment.
Abstract
Description
______________________________________ Average plasma β-carotene level (μg/100 ml) Group Day 0 Day 1 Day 2 Day 4 Day 32 ______________________________________ 1 230 1,547 1,705 1,214 369 2 221 288 371 355 232 3 182 183 191 204 207 ______________________________________
Claims (10)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19803048000 DE3048000A1 (en) | 1980-12-19 | 1980-12-19 | STABLE INJECTABLE (BETA) CAROTINE SOLUBILISATES AND METHOD FOR THE PRODUCTION THEREOF |
DE3048000 | 1980-12-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
US4435427A true US4435427A (en) | 1984-03-06 |
Family
ID=6119676
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/329,124 Expired - Lifetime US4435427A (en) | 1980-12-19 | 1981-12-09 | Stable injectable β-carotene micellar solutions and their preparation |
Country Status (7)
Country | Link |
---|---|
US (1) | US4435427A (en) |
EP (1) | EP0055817B1 (en) |
CA (1) | CA1185185A (en) |
CS (1) | CS228528B2 (en) |
DE (2) | DE3048000A1 (en) |
ES (1) | ES508145A0 (en) |
HU (1) | HU185159B (en) |
Cited By (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4680314A (en) * | 1985-08-30 | 1987-07-14 | Microbio Resources, Inc. | Process for producing a naturally-derived carotene/oil composition by direct extraction from algae |
US5260340A (en) * | 1992-11-19 | 1993-11-09 | Baranowitz Steven A | Prevention and amelioration of acetaminophen toxicity with beta-carotene |
US5453447A (en) * | 1990-10-02 | 1995-09-26 | Basf Aktiengesellschaft | Preparation of stable injectable β-carotene solubilizates |
AU671152B2 (en) * | 1992-09-15 | 1996-08-15 | Smithkline Beecham Plc | Novel compositions |
US5895659A (en) * | 1993-03-11 | 1999-04-20 | Basf Akteingesellschaft | Finely dispersed carotenoid and retinoid suspension and their preparation |
US6007856A (en) * | 1997-08-08 | 1999-12-28 | The Procter & Gamble Company | Oil-in-water dispersions of β-carotene and other carotenoids stable against oxidation prepared from water-dispersible beadlets having high concentrations of carotenoid |
US6093348A (en) * | 1996-05-14 | 2000-07-25 | Roche Vitamins Inc. | Process for manufacture of carotenoid compositions |
US6261598B1 (en) | 1998-08-26 | 2001-07-17 | Basf Aktiengesellschaft | Carotenoid formulations, comprising a mixture of B-carotens, lycopene and lutein |
US6271396B1 (en) | 1998-07-16 | 2001-08-07 | Basf Aktiengesellschaft | Use of organosulfur compounds for effecting a bathocromic shift in the UV/vis absorption bands of carotenoids |
US6287615B1 (en) | 1996-12-20 | 2001-09-11 | Basf Aktiengesellschaft | Use of solubilized carotenoid preparations for coloring food preparations |
WO2002085328A2 (en) * | 2001-02-11 | 2002-10-31 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Method for producing an active ingredient concentrate, and an active ingredient concentrate |
US20040162329A1 (en) * | 2002-07-29 | 2004-08-19 | Lockwood Samuel Fournier | Structural carotenoid analogs for the inhibition and amelioration of disease |
US20050004235A1 (en) * | 2002-07-29 | 2005-01-06 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for the inhibition and amelioration of liver disease |
US20050009930A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for controlling connexin 43 expression |
US20050009788A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid ester analogs or derivatives for controlling connexin 43 expression |
US20050009758A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US20050026874A1 (en) * | 2002-07-29 | 2005-02-03 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for the inhibition and amelioration of liver disease |
US20050049248A1 (en) * | 2002-07-29 | 2005-03-03 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for controlling C-reactive protein levels |
US20050059635A1 (en) * | 2002-07-29 | 2005-03-17 | Lockwood Samuel Fournier | Carotenoid ester analogs or derivatives for controlling C-reactive protein levels |
US20050059659A1 (en) * | 2002-07-29 | 2005-03-17 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for controlling C-reactive protein levels |
US20050065096A1 (en) * | 2002-07-29 | 2005-03-24 | Lockwood Samuel Fournier | Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US20050075316A1 (en) * | 2002-07-29 | 2005-04-07 | Lockwood Samuel Fournier | Pharmaceutical compositions including carotenoid ester analogs or derivatives for the inhibition and amelioration of disease |
US20050090469A1 (en) * | 2002-07-29 | 2005-04-28 | Lockwood Samuel F. | Carotenoid ester analogs or derivatives for the inhibition and amelioration of liver disease |
US20050113372A1 (en) * | 2002-07-29 | 2005-05-26 | Lockwood Samuel F. | Carotenoid analogs or derivatives for the inhibition and amelioration of disease |
US20050143475A1 (en) * | 2002-07-29 | 2005-06-30 | Lockwood Samuel F. | Carotenoid analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury |
US20050148517A1 (en) * | 2002-07-29 | 2005-07-07 | Lockwood Samuel F. | Carotenoid ether analogs or derivatives for controlling connexin 43 expression |
US20050261254A1 (en) * | 2004-04-14 | 2005-11-24 | Lockwood Samuel F | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
US20060058269A1 (en) * | 2004-04-14 | 2006-03-16 | Lockwood Samuel F | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
US20060088905A1 (en) * | 2004-10-01 | 2006-04-27 | Lockwood Samuel F | Methods for the synthesis of zeazanthin |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3048000A1 (en) * | 1980-12-19 | 1982-07-15 | Basf Ag | STABLE INJECTABLE (BETA) CAROTINE SOLUBILISATES AND METHOD FOR THE PRODUCTION THEREOF |
US5686488A (en) * | 1995-08-25 | 1997-11-11 | Alcon Laboratories, Inc. | Polyethoxylated castor oil products as anti-inflammatory agents |
DE19609477A1 (en) * | 1996-03-11 | 1997-09-18 | Basf Ag | Stable aqueous solubilisates of carotenoids and vitamins |
DE19609476A1 (en) * | 1996-03-11 | 1997-09-18 | Basf Ag | Stable parenteral administration suitable carotenoid emulsions |
AT408186B (en) * | 1998-12-15 | 2001-09-25 | Sanochemia Pharmazeutika Ag | AQUEOUS PREPARATION OF BETA CAROTINE |
DE102005032352A1 (en) * | 2005-07-08 | 2007-01-11 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Solubilizer for an active ingredient concentrate in the food industry comprises a St. John's wort extract, a roseda extract or a tarragon extract, a polysorbate emulsifier and water |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1210127B (en) | 1963-11-01 | 1966-02-03 | Hoffmann La Roche | Process for stabilizing aqueous solutions containing lipophilic substances |
DE2236899A1 (en) | 1972-07-27 | 1974-02-07 | Philips Patentverwaltung | Water-miscible carotenoid emulsions - contg tris(hydroxymethyl) amino methane soaps as emulsifiers |
US3998753A (en) | 1974-08-13 | 1976-12-21 | Hoffmann-La Roche Inc. | Water dispersible carotenoid preparations and processes thereof |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2417299A (en) * | 1943-08-06 | 1947-03-11 | Us Vitamin Corp | Fat-soluble vitamin solutions |
US2518230A (en) * | 1947-11-15 | 1950-08-08 | Us Vitamin Corp | Aqueous solutions of lipoid-soluble vitamins |
US2524247A (en) * | 1948-07-10 | 1950-10-03 | Hoffmann La Roche | Aqueous solutions of lipoid-soluble vitamins |
DE970772C (en) * | 1951-06-05 | 1958-10-30 | Wander Ag Dr A | Process for the production of aqueous, in particular concentrated aqueous solutions of vitamins D and / or D. |
DE2526938C2 (en) * | 1975-02-14 | 1982-04-22 | F. Hoffmann-La Roche & Co. AG, 4002 Basel | Vitamin preparations |
DE3048000A1 (en) * | 1980-12-19 | 1982-07-15 | Basf Ag | STABLE INJECTABLE (BETA) CAROTINE SOLUBILISATES AND METHOD FOR THE PRODUCTION THEREOF |
-
1980
- 1980-12-19 DE DE19803048000 patent/DE3048000A1/en not_active Withdrawn
-
1981
- 1981-10-29 DE DE8181109220T patent/DE3175119D1/en not_active Expired
- 1981-10-29 EP EP81109220A patent/EP0055817B1/en not_active Expired
- 1981-12-07 CA CA000391630A patent/CA1185185A/en not_active Expired
- 1981-12-09 US US06/329,124 patent/US4435427A/en not_active Expired - Lifetime
- 1981-12-18 HU HU813873A patent/HU185159B/en not_active IP Right Cessation
- 1981-12-18 CS CS819510A patent/CS228528B2/en unknown
- 1981-12-18 ES ES508145A patent/ES508145A0/en active Granted
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1210127B (en) | 1963-11-01 | 1966-02-03 | Hoffmann La Roche | Process for stabilizing aqueous solutions containing lipophilic substances |
GB1041890A (en) | 1963-11-01 | 1966-09-07 | Hoffmann La Roche | Novel lipophilic preparations and the manufacture thereof |
US3436459A (en) | 1963-11-01 | 1969-04-01 | Hoffmann La Roche | Fat soluble vitamin compositions |
DE2236899A1 (en) | 1972-07-27 | 1974-02-07 | Philips Patentverwaltung | Water-miscible carotenoid emulsions - contg tris(hydroxymethyl) amino methane soaps as emulsifiers |
US3998753A (en) | 1974-08-13 | 1976-12-21 | Hoffmann-La Roche Inc. | Water dispersible carotenoid preparations and processes thereof |
Cited By (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4680314A (en) * | 1985-08-30 | 1987-07-14 | Microbio Resources, Inc. | Process for producing a naturally-derived carotene/oil composition by direct extraction from algae |
US5453447A (en) * | 1990-10-02 | 1995-09-26 | Basf Aktiengesellschaft | Preparation of stable injectable β-carotene solubilizates |
AU671152B2 (en) * | 1992-09-15 | 1996-08-15 | Smithkline Beecham Plc | Novel compositions |
US5607707A (en) * | 1992-09-15 | 1997-03-04 | Smithkline Beecham P.L.C. | Compositions |
US5260340A (en) * | 1992-11-19 | 1993-11-09 | Baranowitz Steven A | Prevention and amelioration of acetaminophen toxicity with beta-carotene |
US5670549A (en) * | 1992-11-19 | 1997-09-23 | Baranowitz; Steven | Prevention and amelioration of liver toxicity with beta-carotene |
US5895659A (en) * | 1993-03-11 | 1999-04-20 | Basf Akteingesellschaft | Finely dispersed carotenoid and retinoid suspension and their preparation |
US6093348A (en) * | 1996-05-14 | 2000-07-25 | Roche Vitamins Inc. | Process for manufacture of carotenoid compositions |
US6287615B1 (en) | 1996-12-20 | 2001-09-11 | Basf Aktiengesellschaft | Use of solubilized carotenoid preparations for coloring food preparations |
US6007856A (en) * | 1997-08-08 | 1999-12-28 | The Procter & Gamble Company | Oil-in-water dispersions of β-carotene and other carotenoids stable against oxidation prepared from water-dispersible beadlets having high concentrations of carotenoid |
US6271396B1 (en) | 1998-07-16 | 2001-08-07 | Basf Aktiengesellschaft | Use of organosulfur compounds for effecting a bathocromic shift in the UV/vis absorption bands of carotenoids |
US6261598B1 (en) | 1998-08-26 | 2001-07-17 | Basf Aktiengesellschaft | Carotenoid formulations, comprising a mixture of B-carotens, lycopene and lutein |
WO2002085328A2 (en) * | 2001-02-11 | 2002-10-31 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Method for producing an active ingredient concentrate, and an active ingredient concentrate |
WO2002085328A3 (en) * | 2001-02-11 | 2003-11-06 | Aquanova Ger Solubilisate Tech | Method for producing an active ingredient concentrate, and an active ingredient concentrate |
US20040081670A1 (en) * | 2001-02-11 | 2004-04-29 | Dariush Behnam | Method for producing an active ingredient concentrate, and an active ingredient concentrate |
JP2006241167A (en) * | 2001-02-11 | 2006-09-14 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Method for producing active ingredient concentrate and active ingredient concentrate |
US20050065096A1 (en) * | 2002-07-29 | 2005-03-24 | Lockwood Samuel Fournier | Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US20050075316A1 (en) * | 2002-07-29 | 2005-04-07 | Lockwood Samuel Fournier | Pharmaceutical compositions including carotenoid ester analogs or derivatives for the inhibition and amelioration of disease |
US20050009930A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for controlling connexin 43 expression |
US20050009788A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid ester analogs or derivatives for controlling connexin 43 expression |
US20050009758A1 (en) * | 2002-07-29 | 2005-01-13 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US20050026874A1 (en) * | 2002-07-29 | 2005-02-03 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for the inhibition and amelioration of liver disease |
US20050037995A1 (en) * | 2002-07-29 | 2005-02-17 | Lockwood Samuel Fournier | Carotenoid ester analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury |
US20050049248A1 (en) * | 2002-07-29 | 2005-03-03 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for controlling C-reactive protein levels |
US20050059635A1 (en) * | 2002-07-29 | 2005-03-17 | Lockwood Samuel Fournier | Carotenoid ester analogs or derivatives for controlling C-reactive protein levels |
US20050059659A1 (en) * | 2002-07-29 | 2005-03-17 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for controlling C-reactive protein levels |
US20040162329A1 (en) * | 2002-07-29 | 2004-08-19 | Lockwood Samuel Fournier | Structural carotenoid analogs for the inhibition and amelioration of disease |
US20050065097A1 (en) * | 2002-07-29 | 2005-03-24 | Lockwood Samuel Fournier | Carotenoid ether analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury |
US20050075337A1 (en) * | 2002-07-29 | 2005-04-07 | Lockwood Samuel Fournier | Pharmaceutical compositions including carotenoid analogs or derivatives for the inhabition and amelioration of disease |
US7317008B2 (en) | 2002-07-29 | 2008-01-08 | Cardax Pharmaceuticals, Inc. | Carotenoid ester analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury |
US20050090469A1 (en) * | 2002-07-29 | 2005-04-28 | Lockwood Samuel F. | Carotenoid ester analogs or derivatives for the inhibition and amelioration of liver disease |
US20050113372A1 (en) * | 2002-07-29 | 2005-05-26 | Lockwood Samuel F. | Carotenoid analogs or derivatives for the inhibition and amelioration of disease |
US20050143475A1 (en) * | 2002-07-29 | 2005-06-30 | Lockwood Samuel F. | Carotenoid analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury |
US20050148517A1 (en) * | 2002-07-29 | 2005-07-07 | Lockwood Samuel F. | Carotenoid ether analogs or derivatives for controlling connexin 43 expression |
US7763649B2 (en) | 2002-07-29 | 2010-07-27 | Cardax Pharmaceuticals, Inc. | Carotenoid analogs or derivatives for controlling connexin 43 expression |
US20050004235A1 (en) * | 2002-07-29 | 2005-01-06 | Lockwood Samuel Fournier | Carotenoid analogs or derivatives for the inhibition and amelioration of liver disease |
US7723327B2 (en) | 2002-07-29 | 2010-05-25 | Cardax Pharmaceuticals, Inc. | Carotenoid ester analogs or derivatives for the inhibition and amelioration of liver disease |
US7592449B2 (en) | 2002-07-29 | 2009-09-22 | Cardax Pharmaceuticals, Inc. | Structural carotenoid analogs for the inhibition and amelioration of disease |
US7521584B2 (en) | 2002-07-29 | 2009-04-21 | Cardax Pharmaceuticals, Inc. | Carotenoid analogs or derivatives for the inhibition and amelioration of disease |
US7375133B2 (en) | 2002-07-29 | 2008-05-20 | Cardax Pharmaceuticals, Inc. | Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US7345091B2 (en) | 2002-07-29 | 2008-03-18 | Cardax Pharmaceuticals, Inc. | Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease |
US7320997B2 (en) | 2002-07-29 | 2008-01-22 | Cardax Pharmaceuticals, Inc. | Pharmaceutical compositions including carotenoid ester analogs or derivatives for the inhibition and amelioration of disease |
US7145025B2 (en) | 2002-07-29 | 2006-12-05 | Hawaii Biotech, Inc. | Structural carotenoid analogs for the inhibition and amelioration of disease |
US20060058269A1 (en) * | 2004-04-14 | 2006-03-16 | Lockwood Samuel F | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
US7691901B2 (en) | 2004-04-14 | 2010-04-06 | Cardax Pharmaceuticals Inc. | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
US20050261254A1 (en) * | 2004-04-14 | 2005-11-24 | Lockwood Samuel F | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
US7247752B2 (en) | 2004-10-01 | 2007-07-24 | Cardax Pharmaceuticals, Inc. | Methods for the synthesis of astaxanthin |
US20060183185A1 (en) * | 2004-10-01 | 2006-08-17 | Lockwood Samuel F | Method for the synthesis of astaxanthin |
US20060178538A1 (en) * | 2004-10-01 | 2006-08-10 | Lockwood Samuel F | Methods for the synthesis of chiral dihydroxy intermediates useful for the chiral synthesis of carotenoids |
US20060167319A1 (en) * | 2004-10-01 | 2006-07-27 | Lockwood Samuel F | Methods for the synthesis of unsaturated ketone intermediates useful for the synthesis of carotenoids |
US20060155150A1 (en) * | 2004-10-01 | 2006-07-13 | Lockwood Samuel F | Methods for the synthesis of lutein |
US20060111580A1 (en) * | 2004-10-01 | 2006-05-25 | Lockwood Samuel F | Methods for the synthesis of chiral dihydroxy ketone intermediates useful for the chiral synthesis of carotenoids |
US20060088904A1 (en) * | 2004-10-01 | 2006-04-27 | Lockwood Samuel F | Methods for the synthesis of astaxanthin |
US20060088905A1 (en) * | 2004-10-01 | 2006-04-27 | Lockwood Samuel F | Methods for the synthesis of zeazanthin |
Also Published As
Publication number | Publication date |
---|---|
EP0055817A3 (en) | 1983-03-30 |
HU185159B (en) | 1984-12-28 |
DE3048000A1 (en) | 1982-07-15 |
ES8300472A1 (en) | 1982-11-01 |
ES508145A0 (en) | 1982-11-01 |
EP0055817B1 (en) | 1986-08-13 |
CS228528B2 (en) | 1984-05-14 |
CA1185185A (en) | 1985-04-09 |
EP0055817A2 (en) | 1982-07-14 |
DE3175119D1 (en) | 1986-09-18 |
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